Universität zu Köln

Filipova, Dilyana ORCID: 0000-0003-3532-9765, Henry, Margit, Rotshteyn, Tamara, Brunn, Anna, Carstov, Mariana, Deckert, Martina, Hescheler, Juergen, Sachinidis, Agapios, Pfitzer, Gabriele and Papadopoulos, Symeon (2018). Distinct transcriptomic changes in E14.5 mouse skeletal muscle lacking RYR1 or Ca(v)1.1 converge at E18.5. PLoS One, 13 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

Full text not available from this repository.

Abstract

In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels-the 1,4-dihydropyridine receptor (Ca(v)1.1) and the type 1 ryanodine receptor (RYR1)-underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+](i) and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Ca(v)1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14.5 -the end of primary myogenesis and around the onset of intrauterine limb movement, and at E18.5 -the end of secondary myogenesis, in WT, RYR1(-/-), and Ca(v)1.1(-/-) murine limb skeletal muscle. At E14.5 the muscle histology of both mutants exhibited initial alterations, which became much more severe at E18.5. Immunohistological analysis also revealed higher levels of activated caspase-3 in the Cav1.1(-/-) muscles at E14.5, indicating an increase in apoptosis. With WT littermates as controls, microarray analyses identified 61 and 97 differentially regulated genes (DEGs) at E14.5, and 493 and 1047 DEGs at E18.5, in RYR1(-/-) and Cav1.1(-/-) samples, respectively. Gene enrichment analysis detected no overlap in the affected biological processes and pathways in the two mutants at E14.5, whereas at E18.5 there was a significant overlap of DEGs in both mutants, affecting predominantly processes linked to muscle contraction. Moreover, the E18.5 vs. E14.5 comparison revealed multiple genotype-specific DEGs involved in contraction, cell cycle and miRNA-mediated signaling in WT, neuronal and bone development in RYR1(-/-), and lipid metabolism in Ca(v)1.1(-/-) samples. Taken together, our study reveals discrete changes in the global transcriptome occurring in limb skeletal muscle from E14.5 to E18.5 in WT, RYR1(-/-) and Ca(v)1.1(-/-) mice. Our results suggest distinct functional roles for RYR1 and Cav1.1 in skeletal primary and secondary myogenesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Filipova, Dilyana UNSPECIFIED orcid.org/0000-0003-3532-9765 UNSPECIFIED Henry, Margit UNSPECIFIED UNSPECIFIED UNSPECIFIED Rotshteyn, Tamara UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunn, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Carstov, Mariana UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfitzer, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulos, Symeon UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-192698
DOI:	10.1371/journal.pone.0194428
Journal or Publication Title:	PLoS One
Volume:	13
Number:	3
Date:	2018
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUSCULAR DYSGENESIS MDG; II-III LOOP; DIHYDROPYRIDINE RECEPTOR; GENE-EXPRESSION; DEVELOPMENTAL GENETICS; RYANODINE RECEPTORS; MICRORNA EXPRESSION; CA2+ RELEASE; MUTATION; CHANNEL Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19269